Fibroblast variants nonresponsive to fibroblast growth factor 1 are defective in its nuclear translocation.
Fibroblast growth factors (FGF) elicit biological effects by binding to high affinity cell-surface receptors and activation of receptor tyrosine kinase. We previously reported that two NIH/3T3 derivatives, NR31 and NR33 (NR cells), express high levels of full-length FGF-1 and exhibit a complete spectrum of transformed phenotype. In the present study, we report that NR cells respond to the mitogenic stimulation of truncated FGF-1 but not to the full-length FGF-1. Incubation of the NR cells with either form of FGF-1 resulted in its binding to cell-surface FGF receptors, activation of mitogen-activated protein (MAP) kinase, and induction of c-fos and c-myc. These data demonstrate that the FGF receptor-mediated, MAP kinase-dependent signaling pathway is not defective in the NR cells. Our data further suggest that the activation of MAP kinase in response to full-length FGF-1 is not sufficient for mitogenesis. Subcellular distribution of exogenously added FGF-1 demonstrated that full-length FGF-1 fails to translocate to the nuclei of NR31 cells. Although the full-length FGF-1 was detected in the nuclear fractions of both NIH/3T3 and NR33 cells, its half-life is much shortened in NR33 than in NIH/3T3 cells. These observations suggest that non-responsiveness of the two NR cell lines may be due to defectiveness at different steps of nuclear translocation mechanism of FGF-1.
Mehta
V B
VB
Department of Internal Medicine, The Ohio State University, Columbus, Ohio 43210, USA.
Connors
L
L
Wang
H C
HC
Chiu
I M
IM
D016475:3T3 Cells; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics; D004789:Enzyme Activation; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010641:Phenotype; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000032:analysis; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
D008934:Mitogens; D010446:Peptide Fragments; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D019000:Phosphotyrosine; D005346:Fibroblast Growth Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases